Intracellular pigment epithelium-derived factor contributes to triglyceride degradation

Zhiyu Dai, Ti Zhou, Cen Li, Weiwei Qi, Yuling Mao, Juling Lu, Yachao Yao, Lei Li, Ting Zhang, Honghai Hong, Shuai Li, Weibin Cai, Zhonghan Yang, Jianxing Ma, Xia Yang*, Guoquan Gao

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity.

Original languageEnglish (US)
Pages (from-to)2076-2086
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
Volume45
Issue number9
DOIs
StatePublished - Jan 1 2013

Keywords

  • ATGL
  • G0S2
  • Hepatocyte
  • Lipid droplet
  • Triglyceride

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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  • Cite this

    Dai, Z., Zhou, T., Li, C., Qi, W., Mao, Y., Lu, J., Yao, Y., Li, L., Zhang, T., Hong, H., Li, S., Cai, W., Yang, Z., Ma, J., Yang, X., & Gao, G. (2013). Intracellular pigment epithelium-derived factor contributes to triglyceride degradation. International Journal of Biochemistry and Cell Biology, 45(9), 2076-2086. https://doi.org/10.1016/j.biocel.2013.07.008